The main aim of this research is to clarify some of the mechanisms underlying porphyrin metabolism; as well as certain aspects of peptide metabolism. A mechanism was proposed for the biosynthesis of uroporphyrinogens from porphobilinogen on the basis of the interaction among 2-aminomethylbilanes by synthesis, and studying their interaction with the enzymatic system, Synthetic methods will be developed for the synthesis of 2-aminomethylpyrroles analogous to porphobilinogen, to find a suitable antimetabolite of porphobilinogen. The interaction of the synthetic pyrroles with porphobilinogen deaminase will be examined. The studies with porphobilinogen oxygenase-the new enzyme of the porphyrin pathway which we have recently discovered-allowed its isolation from human erythrocytes. The relation between this enzyme and porphyrin metabolism will be examined. Variations of the oxygenase in chemically induced porphyrias will be studied. The effect of the diet on the induction of the enzyme will also be examined. Studies with tryptophan pyrrolooxygenase will be performed to establish it as an analytical tool for the specific oxidation of tryptophanyl residues in peptides. Its biological involvement in the inhibition and degradation of tryptophan containing proteins will be studied. Synthetic "isohemins" obtained from isomeric protoporphyrins will be used to study their effect in promoting "isohemoglobin" synthesis in iron deprived rabbit reticulocytes. They will also be bound to globin by using a chemical recombination. The synthetic "isohemins" will also be examined as substrates of heme oxygenase to obtain information about their possible "in vivo" stability.